The architecture of the endoplasmic reticulum (ER) consists of an intricate network of sheets and tubules, but how these domains are generated remains largely unknown. The reticulons and reticulon-like proteins are needed to shape the ER. We have identified proteins with reticulon homology domains the ER in yeast and in higher eukaryotes. These proteins localize to subdomains in the ER in both yeast and mammalian cells. The subdomains are sites of biogenesis of lipid droplets (lipid storage depots) and pre-peroxisomes. Interestingly, the domains are also found at some membrane contact sites, regions where the ER comes in close contact with other organelles. In a second project, we are investigating the role of a conserved family of proteins called FIT proteins in lipid droplet emergence from the ER. In cells lacking the FIT proteins, lipid droplets fail to emerge from the ER, where they initially form. We find that FIT proteins affect levels of the lipid diacylglycerol, which affects lipid droplet association with the ER. This finding led us tot test the model that the spontaneous curvature of lipids in the ER affects lipid droplet emergence from the ER. Preliminary evidence suggests the model is correct.